RNA Interactions Are Essential for CTCF-Mediated Genome Organization.

Animals Binding Sites CCCTC-Binding Factor / chemistry Cell Line Chromatin / chemistry Mice Mouse Embryonic Stem Cells / metabolism Mutation Nucleic Acid Conformation Protein Binding Protein Interaction Domains and Motifs RNA / chemistry Structure-Activity Relationship Transcription, Genetic Zinc Fingers
CTCF RNA binding RNA deficient-mutants TADs chromatin domains chromatin loops chromatin organization gene expression transcriptional inhibition

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
07 11 2019
Historique:
received: 29 01 2019
revised: 15 07 2019
accepted: 16 08 2019
pubmed: 17 9 2019
medline: 26 2 2020
entrez: 17 9 2019
Statut: ppublish

Résumé

The function of the CCCTC-binding factor (CTCF) in the organization of the genome has become an important area of investigation, but the mechanisms by which CTCF dynamically contributes to genome organization are not clear. We previously discovered that CTCF binds to large numbers of endogenous RNAs, promoting its self-association. In this regard, we now report two independent features that disrupt CTCF association with chromatin: inhibition of transcription and disruption of CTCF-RNA interactions through mutations of 2 of its 11 zinc fingers that are not required for CTCF binding to its cognate DNA site: zinc finger 1 (ZF1) or zinc finger 10 (ZF10). These mutations alter gene expression profiles as CTCF mutants lose their ability to form chromatin loops and thus the ability to insulate chromatin domains and to mediate CTCF long-range genomic interactions. Our results point to the importance of CTCF-mediated RNA interactions as a structural component of genome organization.

Identifiants

DOI: 10.1016/j.molcel.2019.08.015 PMID: 31522988 PMC: PMC7195841
pubmed: 31522988
pii: S1097-2765(19)30654-9
doi: 10.1016/j.molcel.2019.08.015
pmc: PMC7195841
mid: NIHMS1068119
pii:
doi:

Substances chimiques

CCCTC-Binding Factor 0
Chromatin 0
Ctcf protein, mouse 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

412-422.e5

Subventions

Organisme : NCI NIH HHS
ID : R01 CA199652
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016087
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS100897
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122515
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Ricardo Saldaña-Meyer (R)

Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY, USA. Electronic address: ricardo.saldana-meyer@nyulangone.org.

Javier Rodriguez-Hernaez (J)

Department of Pathology, NYULSoM, New York, NY, USA.

Thelma Escobar (T)

Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY, USA.

Mayilaadumveettil Nishana (M)

Department of Pathology, NYULSoM, New York, NY, USA.

Karina Jácome-López (K)

Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Elphege P Nora (EP)

Gladstone Institutes, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.

Benoit G Bruneau (BG)

Gladstone Institutes, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.

Aristotelis Tsirigos (A)

Department of Pathology, NYULSoM, New York, NY, USA; Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, USA.

Mayra Furlan-Magaril (M)

Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Jane Skok (J)

Department of Pathology, NYULSoM, New York, NY, USA.

Danny Reinberg (D)

Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY, USA. Electronic address: danny.reinberg@nyulangone.org.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › RNA Interactions Are Essential for...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › RNA Interactions Are Essential for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Facteur de liaison à la séquence CCCTC › RNA Interactions Are Essential for...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › RNA Interactions Are Essential for...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › RNA Interactions Are Essential for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › RNA Interactions Are Essential for...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches embryonnaires › Cellules souches embryonnaires de souris › RNA Interactions Are Essential for...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › RNA Interactions Are Essential for...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › RNA Interactions Are Essential for...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › RNA Interactions Are Essential for...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Motifs et domaines d'intéraction protéique › RNA Interactions Are Essential for...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › RNA Interactions Are Essential for...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › RNA Interactions Are Essential for...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Transcription génétique › RNA Interactions Are Essential for...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Éléments structuraux des protéines › Doigts de zinc › RNA Interactions Are Essential for...